LIPFENDRA (enlicitide) - CORALreef Lipids

July 15, 2026: Merck (NYSE: MRK) announced FDA approval of LIPFENDRA (enlicitide) tablets 20 mg, an oral macrocyclic peptide PCSK9 inhibitor, as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). The approval is supported by two pivotal Phase 3 trials in the CORALreef program.

CORALreef Lipids (NCT05952856; n=2,904): At week 24 (primary endpoint), LIPFENDRA achieved a placebo-adjusted 56% LDL-C reduction (95% CI -61 to -51; p<0.001), corresponding to a 57% reduction from baseline vs a 3% increase with placebo. Non-HDL-C decreased 54% and ApoB 50% vs placebo. Adverse reactions were similar to placebo.

CORALreef HeFH (NCT05952869; n=303): At week 24, LIPFENDRA produced a placebo-adjusted 59% LDL-C reduction (95% CI -66 to -53; p<0.001), with a 58% reduction from baseline vs a 3% increase with placebo. Non-HDL-C fell 52% and ApoB 48% vs placebo. Diarrhea (7% vs 2%) and dizziness (9% vs 4%) were more common than placebo; discontinuations were similar.

Ongoing/upcoming: CORALreef Outcomes (NCT06008756), a cardiovascular morbidity/mortality outcomes trial, has completed enrollment (>14,500); it is not yet known if LIPFENDRA reduces cardiovascular events. Additional studies include CORALreef Extension, Pediatric, and Combination trials.